Open AccessDifferentiating the Sodium‐Glucose Cotransporter 1 Inhibition Capacity of Canagliflozin vs. Dapagliflozin and Empagliflozin Using Quantitative Systems Pharmacology Modeling
Author(s) -
Sokolov Victor,
Yakovleva Tatiana,
Chu Lulu,
Tang Weifeng,
Greasley Peter J.,
Johansson Susanne,
Peskov Kirill,
Helmlinger Gabriel,
Boulton David W.,
Penland Robert C.
Publication year - 2020
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12498
Subject(s) - empagliflozin , canagliflozin , dapagliflozin , renal glucose reabsorption , excretion , renal function , pharmacology , endocrinology , medicine , type 2 diabetes , urinary system , diabetes mellitus , chemistry
The aim of this research was to differentiate dapagliflozin, empagliflozin, and canagliflozin based on their capacity to inhibit sodium‐glucose cotransporter (SGLT) 1 and 2 in patients with type 2 diabetes using a previously developed quantitative systems pharmacology model of renal glucose filtration, reabsorption, and excretion. The analysis was based on pooled, mean study‐level data on 24‐hour urinary glucose excretion, average daily plasma glucose, and estimated glomerular filtration rate collected from phase I and II clinical trials of SGLT2 inhibitors. Variations in filtered glucose across clinical studies were shown to drive the apparent differences in the glucosuria dose–response relationships among the gliflozins. A normalized dose–response analysis demonstrated similarity of dapagliflozin and empagliflozin, but not canagliflozin. At approved doses, SGLT1 inhibition by canagliflozin but not dapagliflozin or empagliflozin contributed to ~ 10% of daily urinary glucose excretion.